title: Integrated mutation, copy number and expression profiling in resectable non-small cell lung cancer.
abstract: BACKGROUND
  The aim of this study was to identify critical genes involved in non-small cell lung cancer (NSCLC) pathogenesis that may lead to a more complete understanding of this disease and identify novel molecular targets for use in the development of more effective therapies.
  
  
  METHODS
  Both transcriptional and genomic profiling were performed on 69 resected NSCLC specimens and results correlated with mutational analyses and clinical data to identify genetic alterations associated with groups of interest.
  
  
  RESULTS
  Combined analyses identified specific patterns of genetic alteration associated with adenocarcinoma vs. squamous differentiation; KRAS mutation; TP53 mutation, metastatic potential and disease recurrence and survival. Amplification of 3q was associated with mutations in TP53 in adenocarcinoma. A prognostic signature for disease recurrence, reflecting KRAS pathway activation, was validated in an independent test set.
  
  
  CONCLUSIONS
  These results may provide the first steps in identifying new predictive biomarkers and targets for novel therapies, thus improving outcomes for patients with this deadly disease.
authors.affiliation: Department of Oncology, St Vincent's Hospital, (Victoria Pde), Melbourne, (3065), Australia. Genni.Newnham@svhm.org.au
authors.forename: Genni M
authors.initials: GM
authors.lastname: Newnham
authors.forename: Matthew
authors.initials: M
authors.lastname: Conron
authors.forename: Sueanne
authors.initials: S
authors.lastname: McLachlan
authors.forename: Alexander
authors.initials: A
authors.lastname: Dobrovic
authors.forename: Hongdo
authors.initials: H
authors.lastname: Do
authors.forename: Jason
authors.initials: J
authors.lastname: Li
authors.forename: Kenneth
authors.initials: K
authors.lastname: Opeskin
authors.forename: Natalie
authors.initials: N
authors.lastname: Thompson
authors.forename: Gavin M
authors.initials: GM
authors.lastname: Wright
authors.forename: David M
authors.initials: DM
authors.lastname: Thomas
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000782:Aneuploidy; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D018628:Gene Dosage / Q000502:physiology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis